Diagnosis and Treatment of MODY: An Updated Mini Review

Maturity-Onset Diabetes of the Young (MODY) is the most common form of monogenic diabetes resulting from a single gene mutation. It is characterized by mild hyperglycemia, autosomal dominant inheritance, early onset of diabetes (<25 years), insulin resistance, and preservation of endogenous insulin secretion. Currently, 14 MODY subtypes have been identified, with differences in incidence, clinical features, diabetes severity and related complications, and treatment response. This type of diabetes is mostly misdiagnosed as either type 1 or type 2 diabetes mellitus because it is difficult to differentiate between these forms of diabetes due to clinical similarities, the high cost of genetic testing, and lack of awareness. As a result, thousands of patients are not receiving appropriate treatment. Accurate diagnosis would allow for more effective therapeutic management and treatment strategies that are distinct from those used for type 1 and type 2 diabetes. This review serves to explore MODY subtypes, diagnosis, and treatment, and increase awareness of MODY incidence.

Inpatient Glycemic Control With Sliding Scale Insulin in Noncritical Patients With Type 2 Diabetes: Who Can Slide?

OBJECTIVE: Despite clinical guideline recommendations, sliding scale insulin (SSI) is widely used for the hospital management of patients with type 2 diabetes (T2D). We aimed to determine which patients with T2D can be appropriately managed with SSI in non–critical care settings. METHODS: We used electronic health records to assess inpatient glycemic control in medicine and surgical patients treated with SSI according to admission blood glucose (BG) concentration between June 2010 and June 2018. Primary outcome was the percentage of patients with T2D achieving target glycemic control, defined as mean hospital BG 70 to 180 mg/dL without hypoglycemia <70 mg/dL during SSI therapy. RESULTS: Among 25,813 adult patients with T2D, 8,095 patients (31.4%) were treated with SSI. Among patients with admission BG <140 mg/dL and BG 140 to 180 mg/dL, 86% and 83%, respectively, achieved target control without hypoglycemia, as compared with only 18% of those with admission BG ≥250 mg/dL (P < .001). After adjusting for age, gender, body mass index (BMI), race, Charlson Comorbidity Index score, and setting, the odds of poor glycemic control increased with higher admission BG (BG 140-180 mg/dL: odds ratio [OR], 1.8; 95% CI, 1.5-2.2; BG 181-250 mg/dL: OR, 3.7; 95% CI, 3.1-4.4; BG >250 mg/dL: OR, 7.2; 95% CI, 5.8-9.0), as compared with patients with BG <140 mg/dL. A total of 1,192 patients (15%) treated with SSI required additional basal insulin during hospitalization. CONCLUSION: Most non–intensive care unit patients with admission BG <180 mg/dL treated with SSI alone achieve target glycemic control during hospitalization, suggesting that cautious use of SSI may be a viable option for certain patients with mild hyperglycemia.

NGS Analysis Revealed Digenic Heterozygous GCK and HNF1A Variants in a Child with Mild Hyperglycemia: A Case Report

Monogenic diabetes (MD) represents a heterogeneous group of disorders whose most frequent form is maturity-onset diabetes of the young (MODY). MD is predominantly caused by a mutation in a single gene. We report a case of a female patient with suspected MD and a positive family history for diabetes and obesity. In this patient, two gene variants have been identified by next-generation sequencing (NGS): one in the Glucokinase (GCK) gene reported in the Human Gene Mutation Database (HGMD) and in the literature associated with GCK/MODY, and the other in the hepatocyte nuclear factor 1A (HNF1A) gene not previously described. The GCK variant was also identified in the hyperglycemic father, whereas the HNF1A variant was present in the mother. This new case of digenic GCK/HNF1A variants identified in a hyperglycemic subject, evidences the importance of NGS analysis in patients with suspected MD. In fact, this methodology will allow us to both increase the number of diagnoses and to identify mutations in more than one gene, with a better understanding of the genetic cause, and the clinical course, of the disease.

Acute and Chronic Effects of Low-Volume High-Intensity Interval Training Compared to Moderate-Intensity Continuous Training on Glycemic Control and Body Composition in Older Women with Type 2 Diabetes

Objective: To compare the acute and chronic effects of low-volume high-intensity interval training (HIIT) to moderate-intensity continuous training (MICT) on glycemic control, body composition and continuous glucose monitoring (CGM) in older women with type 2 diabetes (T2D). Methods: Thirty older women (68 ± 5 years) with T2D were randomized in two groups—HIIT (75 min/week) or MICT (150 min/week). Glucose homeostasis (A1c, glucose, insulin, HOMA-IR2) and body composition (iDXA) were measured before and after the 12-week exercise intervention. During the first and last week of training (24-h before and 48-h after exercise), the following CGM-derived data were measured: 24-h and peak glucose levels, glucose variability and time spent in hypoglycemia as well as severe and mild hyperglycemia. Results: While lean body mass increased (p = 0.035), total and trunk fat mass decreased (p ≤ 0.007), without any difference between groups (p ≥ 0.81). Fasting glucose levels (p = 0.001) and A1c (p = 0.014) significantly improved in MICT only, with a significant difference between groups for fasting glucose (p = 0.02). Neither HIIT nor MICT impacted CGM-derived data at week 1 (p ≥ 0.25). However, 24-h and peak glucose levels, as well as time spent in mild hyperglycemia, decreased in HIIT at week 12 (p ≤ 0.03). Conclusion: These results suggest that 12 weeks of low-volume HIIT is enough to provide similar benefit to MICT for body composition and improve the acute effect of exercise when measured with CGM.

Atherogenic Index Reduction and Weight Loss in Metabolic Syndrome Patients Treated with A Novel Pectin-Enriched Formulation of Bergamot Polyphenols

Bergamot flavonoids counteract dyslipidemia and hyperglycemia but fail to induce a significant weight loss. Here, we evaluated the efficacy of bergamot polyphenol extract complex (BPE-C), a novel bergamot juice-derived formulation enriched with flavonoids and pectins, on several metabolic syndrome parameters. Obese patients with atherogenic index of plasma (AIP) over 0.34 and mild hyperglycemia were recruited to a double-blind randomized trial comparing two doses of BPE-C (650 and 1300 mg daily) with placebo. Fifty-two subjects met the inclusion criteria and were assigned to three experimental groups. Fifteen subjects per group completed 90 days-trial. BPE-C reduced significantly fasting glucose by 18.1%, triglycerides by 32% and cholesterol parameters by up to 41.4%, leading to a powerful reduction of AIP (below 0.2) in the high dose group. The homeostasis model assessment of insulin resistance (HOMA-IR) and insulin levels were also reduced. Moreover, BPE-C decreased body weight by 14.8% and body mass index by 15.9% in BPE-C high group. This correlated with a significant reduction of circulating hormones balancing caloric intake, including leptin, ghrelin and upregulation of adiponectin. All effects showed a dose-dependent tendency. This study suggests that food supplements, containing full spectrum of bergamot juice components, such as BPE-C efficiently induce a combination of weight loss and insulin sensitivity effects together with a robust reduction of atherosclerosis risk.